Converting enzyme inhibitor improves forearm reactive hyperemia in essential hypertension.

Endothelial function is known to be impaired in essential hypertensive patients. In this study, we examined whether antihypertensive drugs improve forearm vasodilatory response to reactive hyperemia in 26 patients with essential hypertension (62 +/- 2 years) without diabetes mellitus, hyperlipidemia, coronary heart disease, or cerebrovascular disease. Antihypertensive drugs were never given or were discontinued for at least 4 weeks before the study. Patients were treated with monotherapy of either temocapril (2 or 4 mg, n = 15) or amlodipine (2.5 or 5 mg, n = 11) for 6 months. Forearm blood flow was measured by strain-gauge plethysmography. Vasodilator response to the release of upper arm compression at 300 mm Hg for 5 minutes and to sublingual administration of nitroglycerin (0.3 mg) were assessed. Changes of forearm blood flow response to reactive hyperemia were significantly less in hypertensive patients (99 +/- 18%) than in age-matched normotensive control subjects (150 +/- 22%, P < .01, n = 39). Blood pressure (mm Hg) was similarly decreased by the treatment with temocapril (160 +/- 4/94 +/- 2 to 139 +/- 3/83 +/- 3, P < .001) or amlodipine (165 +/- 5/94 +/- 3 to 141 +/- 4/82 +/- 3, P < .001). Response to nitroglycerin was not changed by either drug. Forearm vasodilatory response to reactive hyperemia was improved by temocapril (102 +/- 20% to 168 +/- 25%, P < .01) but not by amlodipine (97 +/- 16% to 114 +/- 14%, NS). These results indicate that the treatment with the angiotensin-converting enzyme inhibitor temocapril improved forearm vasodilatory response to reactive hyperemia, suggesting its beneficial effect on endothelial function.

[1]  T. Ogihara,et al.  Impaired endothelial function with essential hypertension assessed by ultrasonography. , 1996, American heart journal.

[2]  F. Costa,et al.  Cost-effectiveness calculations from trials , 1996, Journal of Hypertension - Supplement.

[3]  D. Harrison,et al.  Angiotensin II-mediated hypertension in the rat increases vascular superoxide production via membrane NADH/NADPH oxidase activation. Contribution to alterations of vasomotor tone. , 1996, The Journal of clinical investigation.

[4]  F. Locatelli,et al.  Effect of the Angiotensin-Converting–Enzyme Inhibitor Benazepril on the Progression of Chronic Renal Insufficiency , 1996 .

[5]  G. B. John Mancini,et al.  Angiotensin Converting Enzyme Inhibition, with Quinapril, Improves Endothelial Vasomotor Dysfunction in Patients with Coronary Artery Disease: the TREND Study (Trial on REversing ENdothelial Dysfunction) , 1996 .

[6]  R. Nuesch,et al.  Effects of cilazapril on vascular structure and function in essential hypertension. , 1996, Hypertension.

[7]  P. Vanhoutte,et al.  Endothelium-derived relaxing factors and converting enzyme inhibition. , 1995, The American journal of cardiology.

[8]  M. Yen,et al.  Cilazapril reverses endothelium-dependent vasodilator response to acetylcholine in mesenteric artery from spontaneously hypertensive rats. , 1995, American journal of hypertension.

[9]  E. Schiffrin,et al.  Comparison of effects of angiotensin I-converting enzyme inhibition and beta-blockade for 2 years on function of small arteries from hypertensive patients. , 1995, Hypertension.

[10]  A. Quyyumi,et al.  Impaired endothelium-dependent vasodilation in patients with essential hypertension. Evidence that nitric oxide abnormality is not localized to a single signal transduction pathway. , 1995, Circulation.

[11]  T. Lüscher,et al.  Endothelial dysfunction in aorta of the spontaneously hypertensive, stroke-prone rat: effects of therapy with verapamil and trandolapril alone and in combination. , 1994, Journal of cardiovascular pharmacology.

[12]  T Endo,et al.  Role of nitric oxide in reactive hyperemia in human forearm vessels. , 1994, Circulation.

[13]  M. Creager,et al.  Effect of captopril and enalapril on endothelial function in hypertensive patients. , 1994, Hypertension.

[14]  R W Alexander,et al.  Angiotensin II stimulates NADH and NADPH oxidase activity in cultured vascular smooth muscle cells. , 1994, Circulation research.

[15]  J. Ritter,et al.  Preserved endothelium-dependent vasodilatation in patients with essential hypertension. , 1994, The New England journal of medicine.

[16]  A. Quyyumi,et al.  Effect of antihypertensive treatment on endothelium-dependent vascular relaxation in patients with essential hypertension. , 1993, Journal of the American College of Cardiology.

[17]  A. Quyyumi,et al.  Role of Endothelium‐Derived Nitric Oxide in the Abnormal Endothelium‐Dependent Vascular Relaxation of Patients With Essential Hypertension , 1993, Circulation.

[18]  J. K. Lloyd,et al.  Non-invasive detection of endothelial dysfunction in children and adults at risk of atherosclerosis , 1992, The Lancet.

[19]  T. Lüscher.  Heterogeneity of endothelial dysfunction in hypertension. , 1992, European heart journal.

[20]  S. Moncada,et al.  Effect of local intra-arterial NG-monomethyl-L-arginine in patients with hypertension: the nitric oxide dilator mechanism appears abnormal. , 1992, Journal of hypertension.

[21]  A. Takeshita,et al.  Captopril improves impaired endothelium-dependent vasodilation in hypertensive patients. , 1992, Hypertension.

[22]  P. Vanhoutte,et al.  Potentiation of endothelium-dependent relaxations to bradykinin by angiotensin I converting enzyme inhibitors in canine coronary artery involves both endothelium-derived relaxing and hyperpolarizing factors. , 1992, Circulation research.

[23]  J. Higaki,et al.  Role of Cardiac Angiotensin II in Isoproterenol‐Induced Left Ventricular Hypertrophy , 1992, Hypertension.

[24]  N. Flavahan.  Atherosclerosis or lipoprotein-induced endothelial dysfunction. Potential mechanisms underlying reduction in EDRF/nitric oxide activity. , 1992, Circulation.

[25]  T. Ogihara,et al.  Possible role of the vascular renin-angiotensin system in hypertension and vascular hypertrophy. , 1992, Hypertension.

[26]  K. Pennert,et al.  Reversal of left ventricular hypertrophy in hypertensive patients. A metaanalysis of 109 treatment studies. , 1992, American journal of hypertension.

[27]  R. Tallarida,et al.  Pharmacological evidence that captopril possesses an endothelium-mediated component of vasodilation: effect of sulfhydryl groups on endothelium-derived relaxing factor. , 1991, The Journal of pharmacology and experimental therapeutics.

[28]  C. Stier,et al.  Role of Prostanoids in Renin‐Dependent and Renin‐Independent Hypertension , 1991, Hypertension.

[29]  D. Harrison,et al.  Release of Nitrogen Oxides From Cultured Bovine Aortic Endothelial Cells Is Not Impaired by Calcium Channel Antagonists , 1991, Circulation.

[30]  M. Clozel,et al.  Effects of angiotensin converting enzyme inhibitors and of hydralazine on endothelial function in hypertensive rats. , 1990, Hypertension.

[31]  T. Resink,et al.  Stimulation of endothelin mRNA and secretion in rat vascular smooth muscle cells: a novel autocrine function. , 1990, Cell regulation.

[32]  A. Quyyumi,et al.  Abnormal endothelium-dependent vascular relaxation in patients with essential hypertension. , 1990, The New England journal of medicine.

[33]  T. Lüscher,et al.  Indirect evidence for release of endothelium-derived relaxing factor in human forearm circulation in vivo. Blunted response in essential hypertension. , 1990, Circulation.

[34]  B. Pannier,et al.  Flow-dependent vasodilation of brachial artery in essential hypertension. , 1990, The American journal of physiology.

[35]  S. Snyder,et al.  Isolation of nitric oxide synthetase, a calmodulin-requiring enzyme. , 1990, Proceedings of the National Academy of Sciences of the United States of America.

[36]  P. Vanhoutte.  Endothelium and Control of Vascular Function State of the Art Lecture , 1989, Hypertension.

[37]  A. Mark,et al.  Flow-mediated and reflex changes in large peripheral artery tone in humans. , 1989, Circulation.

[38]  K. Swedberg,et al.  Effects of enalapril on mortality in severe congestive heart failure: results of the Cooperative North Scandinavian Enalapril Survival Study (CONSENSUS). , 1988, The American journal of cardiology.

[39]  A. Sollevi,et al.  The role of myogenic relaxation, adenosine and prostaglandins in human forearm reactive hyperaemia. , 1987, The Journal of physiology.

[40]  R. Ross.  The pathogenesis of atherosclerosis--an update. , 1986, The New England journal of medicine.

[41]  R Busse,et al.  Crucial role of endothelium in the vasodilator response to increased flow in vivo. , 1986, Hypertension.

[42]  P. Vanhoutte,et al.  The calcium agonists Bay K 8644 and (+)202,791 stimulate the release of endothelial relaxing factor from canine femoral arteries. , 1985, European journal of pharmacology.

[43]  T. Stone,et al.  The release of endothelium-derived relaxant factor is calcium dependent. , 1985, Blood vessels.

[44]  R. Furchgott,et al.  The obligatory role of endothelial cells in the relaxation of arterial smooth muscle by acetylcholine , 1980, Nature.

[45]  R. Ross,et al.  The pathogenesis of atherosclerosis (first of two parts). , 1976, The New England journal of medicine.

[46]  D. Eugene Hokanson,et al.  An Electrically Calibrated Plethysmograph for Direct Measurement of Limb Blood Flow , 1975, IEEE Transactions on Biomedical Engineering.

[47]  W. Sterling Edwards,et al.  Blood Vessels , 1959 .